The proposed studies will explore biochemical, behavioral, and genetic interactions between ethanol and cholinergic drugs, most notably nicotine and oxotremorine. These studies will attempt to test the hypothesis that some of ethanol's acute and chronic effects are mediated via effects on nicotinic and muscarinic receptors. The experiments will assess the effects of acute and chronic ethanol treatment on nicotinic and muscarinic receptors as well as the effect of altering these receptors on acute response to ethanol, tolerance to ethanol, and the ethanol withdrawal syndrome. A battery of tests has been developed to measure acute responses to ethanol, nicotine, and oxotremorine as well as tolerance to ethanol and the ethanol withdrawal syndrom. Nicotine, scopolamine, or oxotremorine will be infused into LS and SS mice, two selected lines of mice that differ in acute response to ethanol, and the influence of the resultant receptor changes on ethanol response will be measured. In addition, the effects of ethanol, in vitro and in vivo, on cholinergic receptors will be measured. Finally, the genetic control of ethanol/nicotine and ethanol/oxotremorine interactions will be estimated. These studies should provide added insight into the reasons for simultaneous use and abuse of alcohol and nicotine.